Imaging diagnosis techniques such as those based on PET or MRI have been widely used as methods for diagnosing cancers in recent years. However, by means of these techniques, it is difficult to find microcarcinomas not larger than 1 cm.
Moreover, these techniques also have problems that very large scale instruments are required for imaging, and they are not suitable as diagnostic methods for identifying a cancerous lesion to be excised by a surgeon during surgery, endoscopy, or the like.
A cancer imaging method utilizing a probe complex consisting of a combination of an antibody against a cancer and a pH-sensitive fluorescent probe has recently been reported (Nat. Med., 15, pp. 104-109, 2009). This method has a characteristic feature in that specific imaging of a cancerous tissue with fluorescence is achievable.
However, this method has problems that sensitivity of the probe complex used in this method is insufficient, and that a time of 1 hour or longer is required before a cancerous lesion becomes detectable after the administration of the probe. From these reasons, the method has not yet been practically used as a method for prompt diagnosis of a cancerous tissue during surgery or the like.
As fluorescent probes utilizing a xanthene structure, fluorescent probes for measurement of protease having superior quick responsiveness and quantifiability have been developed, and as a fluorescent probe that specifically reacts with γ-glutamyltransferase (GGT) to give intense fluorescence within a short time, γ-Glu-RhoHM
has also been reported (Masayo Sakabe, “Development of novel fluorescent probes for enzyme activity detection utilizing ring opening for the basis of fluorescence control”, Master's thesis in Graduate School of Pharmaceutical Sciences, The University of Tokyo, presented in the Master's thesis presentation meeting on Mar. 5, 2009, Abstract is readable in The Library of Faculty of Pharmaceutical Sciences, The University of Tokyo). However, use of this fluorescent probe for cancer diagnosis has not yet been reported.
In addition, it has been reported that promotion of expression of γ-glutamyltransferase is observed in cancer cells, and this expression promotion relates to drug resistance (Biochemical Pharmacology, 71, pp. 231-238, 2006). However, any diagnostic method for identifying a cancer cell or a cancerous tissue with high accuracy by detecting γ-glutamyltransferase has not been reported so far.